Expert Analysis

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Study Aim:
To study how the AHA/ACC atherosclerotic cardiovascular disease (ASCVD) risk score performs among four different race/ethnic groups (White, Black, Chinese, and Hispanic) using data from the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. Some authors of the ASCVD risk estimation guideline group previously stated that the overestimation is attributable to the inclusion of Chinese and Hispanics, since the derivation cohort for the ASCVD risk estimator does not include adults of these ethnicities. Another suggestion is that MESA is not representative because it is a highly treated population (with aspirin, anti-hypertensive agents, and statins).

Methods:
The investigators included 6,441 participants aged between 45-79 years from MESA, a prospective community-based cohort. MESA participants were compared with National Health and Nutrition Examination Survey (NHANES) 2013-2014 data to evaluate applicability of the cohort to the US population. The ASCVD risk score was calculated using baseline MESA data from 2000-2002, and expected and observed cardiovascular events in each race/ethnicity and sex were compared in 10-year follow-up. To ascertain the impact of each risk factor on the difference between observed events and expected events based on ASCVD, univariable and multivariable absolute risk regression was performed.

Among MESA participants, the ASCVD risk score overestimated cardiovascular events in both women (predicted events 9%; observed events 4%) and men (predicted events 14%; observed events 7%), with the risk score predicting approximately twice the number of observed events. The overestimation was seen in all four race/ethnic groups (discordance range from 67% in Hispanic men up to 314% in Chinese men).

In multivariable analyses, higher age, Chinese ethnicity, systolic blood pressure, alcohol use, diabetes, exercise, lipid-lowering therapy, and aspirin therapy were associated with risk overestimation (p < 0.05). Estimation of the ASCVD Cox model in MESA leads to significantly different coefficients for each of the variables included in the risk score.

Conclusions:
The investigators conclude that the ASCVD risk score significantly overestimates cardiovascular events in all four race/ethnic groups and in both genders in the MESA study. This study confirms that that the ASCVD risk score often overestimates an older adult's contemporary risk for myocardial infarction (MI) or stroke. Thus, it is important that clinicians and patients enter into a detailed risk discussion before embarking on pharmacologic therapy.

Perspective:
This study elaborates on previous reports that the ASCVD risk score applied to other cohorts may overestimate cardiovascular events.1-3 Several concerns had been raised of previous reports of potential overestimation:

Lack of active surveillance for cardiovascular events in addition to self-reported hospitalizations.

Inclusion of race/ethnic minorities, as overestimation may only be observed in Chinese and Hispanics who were not included in the pooled cohorts used to derive the ASCVD risk score.

More intensive preventive pharmacotherapy such as use of statin therapy, aspirin, anti-hypertensive agents, especially due to the availability of additional risk stratification data, e.g., coronary artery calcium, which was not available in prior cohort studies.

Increased use of revascularization procedures for unstable angina which may reduce hard MI events.

The authors tried to address several of these previous concerns. The MESA study classifies cardiovascular events through several methods in addition to participant reports (death certificates, hospitalization records, autopsy, and from physicians, relatives or friends for out-of-hospital deaths).4 The investigators also adjudicated possible missed events by crosslinking with the CMS database with no meaningful change in their results.

This study reports that the overestimation of events by the ASCVD risk score was present in White, Black, Chinese and Hispanics and not limited to specific ethnicities. Importantly, the authors were able to demonstrate that the MESA study population and natural history was similar to the wider American population by comparing data with NHANES. An alternative possibility is that the derivation cohort participants may not adequately/fully represent the modern American population, helping to explain the discordance seen between the observed and expected events in their multicultural cohort.

One other criticism of the MESA study can be that the participants underwent coronary artery calcium scoring which may have led to both individual and physician behavior change resulting in lower number of events. However, this study reported limited baseline testing data to the MESA participants. Additionally, although it is still possible that lifestyle advice and changes by physicians and participants were more aggressively pursued than in the general population, the authors do demonstrate that anti-hypertensive and lipid lowering treatment were comparable between the MESA study and NHANES data.

In addition, the investigators identified several risk factors that are associated with risk overestimation. The risk factors were higher age (most important), Chinese ethnicity, systolic blood pressure, alcohol use, diabetes, exercise, lipid-lowering therapy, and aspirin therapy. In MESA the relationship of risk factors to cardiovascular events was significantly different than in the ASCVD derivation cohort. These findings are consistent with other reports, for example recent published data from the Framingham Heart Study show that the prevalence of risk factors have changed over the decades.5

The use of invasive therapy has increased over the past 15 years. However, in the Women's Health Study (after accounting for revascularization) there was still an overestimation of events by the ASCVD risk score.6 In addition, although the number of acute myocardial infarctions have decreased according to NHANES data driven by a decrease in mainly STEMI, the number of NSTEMIs have remained stable between 2002-2011.7,8 In addition, including revascularizations of unstable angina in the MESA study as events would still likely lead to overestimation by the ASCVD risk score.9

This report adds to the ongoing concerns for the use of 2013 ASCVD risk score. However, other studies comparing the ASCVD risk score based approach versus an approach using the enrollment criteria of major trials or a hybrid approach have reported that the ASCVD risk score based approach performs the best in identifying patients to treat.10 Thus, although the ASCVD risk score often overestimates risk, currently it provides a useful guide to undertake a primary prevention strategy with clinicians and patients engaging in a discussion of the treatment plan as recommended by the AHA/ACC guidelines.11-13

These discussions of management strategies particularly for individuals with an ASCVD risk score of 5-15% could also be guided by the measurement of coronary artery calcium and lipoprotein(a).14-16 In addition, clinicians should note that the ASCVD risk estimator does highlight (when you select "Other") that the model may significantly under- or overestimate in other race/ethnic groups. The development of a better risk prediction tool needs to use newer risk factor and outcomes data, and include data from multiple races/ethnic groups that are representative of the American population.